Strains of saccharomyces cerevisiae (yeast) carrying a small double-stranded RNA species (the killer plasmid) secrete a glycoprotein toxin which is lethal only to strains not carrying this plasmid. We have located 11 chromosomal genes needed to maintain or replicate the killer plasmid. We have observed bypass of the need for these chromosomal genes by other changes (called KRB for killer replication bypass). In some instances these changes are dominant single-site changes at chromosome centromeres which are unstable to heat. Other KRB changes are unstable $ to mating and result in changes of the ds RNA species present in the cell.